Natural product research during the last few decades has yielded thousands of novel organic compounds from the marine environment. The bioassays guiding these isolations typically have been antimicrobial, antitumor, antiviral or antiinflammatory. Little has been done to explore the oceans for compounds with activity against HIV, AIDS OI including TB, and other infectious diseases. Additionally, because of the limits associated with the conventional self-contained underwater breathing apparatus (SCUBA), the majority of the compounds characterized from the marine environment are the result of shallow water collections (-30 m). Improvements in underwater life support systems have provided marine scientists new mechanisms for collecting from unexplored regions and depths. Closed circuit Underwater Breathing Apparatus (CCUBA) allows a collector to extend the depth and time spent on a dive significantly beyond the limitations imposed by diving with conventional SCUBA. The active component(s) of those extracts showing promising activity against infectious targets will be isolated using preparative and semi-preparative high pressure liquid chromatography (HPLC), independently and interfaced with NMR and FTMS. Marine natural product ligands for HIV-1 integrase will be identified using NOE-pumping experiments. The chemical structures of the biologically active secondary metabolites will be determined with the use of FTMS and 2D NMR. Methods for providing sufficient quantities for in vivo testing via synthesis, semi-synthesis or reisolation will be addressed for promising lead compounds. Lead optimization studies will be conducted utilizing chemical and microbial transformations for biologically active secondary metabolites combined with molecular modeling studies. In the last several decades the oceans have provided some of the most unusual and bioactive chemical structures ever identified. These unusual chemotypes will eventually become important drugs for the treatment and cure of infectious diseases. Beyond serving as viable leads for the treatment of infectious disease the detailed analysis of new active vs. inactive natural products will provide valuable new antiinfective pharmacophores. These Anti-HIV and AIDS-OI pharmacophores may then be used to develop sophisticated antiinfective libraries using combinatorial or parallel synthesis.